Self-Study Modules
 

on Tuberculosis, 1-5
 

Centers for Disease Control and Prevention
 

Division of Tuberculosis Elimination
 

2016
 

Self-Study Modules
 

on Tuberculosis
 

Transmission and 

Pathogenesis of 

Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis 3 

Module 1: Overview 

•	 History of TB 

•	 TB Transmission 

•	 Drug-Resistant TB 

•	 TB Pathogenesis 

•	 Progression from LTBI to TB disea se 

•	 Sites of TB dise ase 

•	 TB Classification System 

•	 Case Studies 

Module 1 – Transmission and Pathogenesis of Tuberculosis 5 

CDC Self-Study Modules on
 

Tuberculosis, 1-5
 

•	 Module 1: Transmission and Pathoge nesis of TB 

•	 Module 2: Epidemiology of TB 

•	 Module 3: Targeted Testing and the Diagnosis of 

Latent TB Infec tion and TB Dis ease 

•	 Module 4: Treatment of Latent TB Infe ction and 

TB Disease 

•	 Module 5: Infectiousness and Infection Control 

Module 1 – Transmission and Pathogenesis of Tuberculosis 2 

Module 1: Objectives 

At completion of this module, learners will be 

able to 

1.	 Describe the history of tuberculosis (TB). 

2.	 Explain how TB is spread (transmission). 

3.	 Define drug-resistant TB. 

4.	 Explain the difference between latent TB infection 

(LTBI) and TB disease. 

5.	 Explain how LTBI and TB disease develop 

(pathogenesis). 

6.	 Describe the classification system for TB. 

Module 1 – Transmission and Pathogenesis of Tuberculosis 4 

History of TB
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 6 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

1
 
 

 

 

 

 

 

 

 

 

 

 

 

History of TB (1) 

•	 TB has affected 

humans for millennia 

•	 Historically known by 

a variety of names, 

including: 

– Consumption 

– Wasting disease 

– White plague 

•	 TB was a death 

sentence for many 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

7 

Vintage image circa 1919
 

Image credit: National Library of Medicine
 

History of TB (2) 

Scientific Discoveries in 1800s 

• Until mid-1800s, many 

believed TB was 

hereditary 

• 1865 Jean AntoineVillemin showed TB 

was contagious 

• 1882 Robert Koch discovered M. 

tuberculosis, the 

bacterium that c auses 

TB Module 1 – Transmission and Pathogenesis of Tuberculosis 8 

 

Mycobacterium tuberculosis 

Image credit: Janice Haney Carr 

History of TB (3)
 

Sanatoriums
 

•	 Before TB antibiotics, 

many patients were 

sent to sanatoriums 

•	 Patients followed a 

regimen of bed rest, 

open air, and sunshine 

•	 TB patients who could 

not afford sanatoriums 

often died at home 

Sanatorium patients resting outside 

Module 1 – Transmission and Pathogenesis of Tuberculosis 9 

Breakthrough in the Fight
 

Against TB (1)
 

Drugs that could kill TB 

bacteria were discovered 

in 1940s and 1950s 

•	 Streptomycin (SM) 

discovered in 1943 

•	 Isoniazid (INH) and 

p-aminosalicylic acid (PAS) 

discovered between 1943
 

and 1952
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Breakthrough in the Fight
 

Against TB (2)
 

•	 TB death rates in U.S. began to drop 

dramatically 

•	 Each year, fewer people died from TB 

•	 Most TB sanatoriums in U.S. had closed by 

mid 1970s 

Module 1 – Transmission and Pathogenesis of Tuberculosis 11 Module 1 – Transmission and Pathogenesis of Tuberculosis 12 

TB Resurgence 

• Increase in TB in mid 

1980s 

• Contributing factors: 

– Inadequate funding for TB 

control programs 

– HIV epidemic 

– Increased immigration from 

countries where TB is common

– Spread of TB in homeless 

shelters and correctional 

facilities 

– Increase and spread of 

multidrug-resistant TB March 16, 1992 Newsweek Magazine Cover 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

2
 

10 
TB Prevention and Control Efforts 

•	 Increased governmental funding for TB control 

programs began in 1992 

•	 Number of TB cases declined from 1993 to 2014 No. of Cases 

Year 

Reported TB Cases, U.S., 1982-2014 

Module 1 – Transmission and Pathogenesis of Tuberculosis 13 

TB History Timeline 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

History of TB 

Study Question 1.1 

In what year was each of the following 

discoveries made? 

a.	 TB was shown to be contagious 

b.	 The bacterium that causes TB was discovered 

c.	 The first drug that could kill TB bacteria was 

discovered 

Module 1 – Transmission and Pathogenesis of Tuberculosis 15 

TB Transmission
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Transmission (1) 

Transmission is defined as the spread of an 

organism, such as M. tuberculosis, from one 

person to another. 

Module 1 – Transmission and Pathogenesis of Tuberculosis 17 

TB Transmission (2)
 

Types of Mycobacteria
 

M. tuberculosis 

•	 M. tuberculosis causes 

most TB cases in U.S. 

•	 Mycobacteria that cause 

TB: 

– M. tuberculosis 

– M. bovis 

– M. africanum 

– M. microti 

– M. canetti 

•	 Mycobacteria that do not 

cause TB 

– e.g., M. avium-complex 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

3
 

14 

16 

18 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TB Transmission (3) 

•	 TB is spread person to 

person through the air via 

droplet nuclei 

•	 M. tuberculosis may be 

expelled when an 

infectious person: – Coughs 

– Speaks 

– Sings 

•	 Transmission occurs 

when another person 

inhales droplet nuclei 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Transmission (4) 

Dots in air represent droplet nuc lei containing 

M. tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis 20 

TB Transmission (5) 

•	 Probability that TB will be transmitted depends 

on: 

– Infectiousness of the TB patient 

– Environment in which the exposure occurred 

– Frequency and duration of the exposure 

– Susceptibility (immune status) of the exposed
 

individual
 

•	 The best way to stop transmission is to: 

– Isolate infectious persons 

– Provide treatment to infectious persons as soon as 

possible 

Module 1 – Transmission and Pathogenesis of Tuberculosis 21 

TB Transmission 

Study Question 1.2 

What organism causes TB? 

What are four other tuberculous mycobacteria? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Transmission 

Study Question 1.3 

How is TB spread? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 23 

TB Transmission 

Study Question 1.4 

The probability that TB will be transmitted 

depends on what four factors? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

19 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

4
 

22 

24 
 

 

 

 

 

 

 

- 

- 

 

- 

 

- 

 

 

 

 

 

 

 

 

 

 

 

 

Drug-Resistant TB
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 25 

Drug-Resistant TB (1)
 

• Caused by M. tuberculosis organisms resistant 

to at least one TB treatment drug 

• Resistant means drugs can no longer kill the 

bacteria 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Drug-Resistant TB (2) 

Mono resistant Resistant to any one TB treatment 

drug 

Poly resistant Resistant to at least any 2 TB drugs 

(but not both isoniazid and rifampin) 

Multidrug 

resistant 

(MDR TB) 

Resistant to at least isoniazid and 

rifampin, the 2 best first-line TB 

treatment drugs 

Extensively 

drug resistant 

(XDR TB) 

Resistant to isoniazid and rifampin, 

PLUS resistant to any fluoroquinolone 

AND at least 1 of the 3 injectable antiTB drugs (e.g., amikacin, kanamycin, 

or capreomycin) 

Module 1 – Transmission and Pathogenesis of Tuberculosis	 27	 Module 1 – Transmission and Pathogenesis of Tuberculosis 28 

Drug-Resistant TB (3) 

Primary 

Resistance 

Caused by person-to-person 

transmission of drug-resistant 

organisms 

Secondary 

Resistance 

(acquired) 

Develops during TB treatment: 

• Patient was not treated with an 

appropriate regimen 

OR 

•	 Patient did not follow treatment 

regimen as prescribed 

Drug-resistant TB 

Study Question 1.5 

What is drug-resistant TB? 

Module 1 – Transmission and Pathogenesis of Tuberculosis	 29	 Module 1 – Transmission and Pathogenesis of Tuberculosis 30 

Drug-resistant TB 

Study Question 1.6 

What is the difference between primary and 

secondary drug resistance? 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

5
 

26 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TB Pathogenesis
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 31 

TB Pathogenesis (1)
 

Pathogenesis is defined as the way an 

infection or disease develops in the body. 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Pathogenesis (2)
 

Latent TB Infection (LTBI)
 

•	 LTBI occurs when tubercle bacilli are in the body, but the immune system is keeping them 

under control 

•	 LTBI is detected by the Mantoux tuberculin skin 

test (TST) or by an interferon-gamma release 

assay (IGRA), such as: 

– QuantiFERON®-TB Gold In-Tube (QFT-GIT) 

– T-Spot®.TB test (T-SPOT) 

•	 People with LTBI are NOT infectious 

Module 1 – Transmission and Pathogenesis of Tuberculosis 33 

TB Pathogenesis (3)
 

TB Disease
 

•	 TB disease develops when the immune 

system cannot keep tubercle bacilli under 

control 

– May develop very soon after infection or 

many years after infection 

•	 About 10% of all people with normal immune 

systems who have LTBI will develop TB 

disease at some point in their lives 

• People with TB disease are often infectious 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis 35 

TB Pathogenesis (4) 

Droplet nuclei c ontaining tubercle bacilli are 

inhaled, enter the lungs, and travel to small 

air sacs (alveoli) 

Module 1 – Transmission and Pathogenesis of Tuberculosis 36 

TB Pathogenesis (5) 

Tubercle bacilli multiply in alveoli, where 

infection begins 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

6
 

32 

34 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Module 1 – Transmission and Pathogenesis of Tuberculosis 37 

TB Pathogenesis (6) 

A small number of tube rcle bacilli enter 

bloodstream and spread throughout body 

Module 1 – Transmission and Pathogenesis of Tuberculosis 38 

TB Pathogenesis (7) 

LTBI 

• Within 2 to 8 weeks the immune system produces 

special immune cells called macrophages that 

surround the tubercle bacilli 

• These cells form a barrier shell that keeps the 

bacilli contained and under control (LTBI) 

TB Pathogenesis (8) 

TB Disease 

• If the immune system CANNOT keep tubercle bacilli 

under control, bacilli begin to multiply rapidly and 

cause TB disease 

• This process can occur in different places in the body 

Module 1 – Transmission and Pathogenesis of Tuberculosis 39 

LTBI vs. TB Disease (1) 

Person with LTBI Person with TB Disease 

(in the lungs) 

• Has a small number of TB 

bacteria in his or her body that are 

alive, but under control 

• Has a large number of active 

TB bacteria in his or her body 

• Cannot spread TB bacteria to 

others 

• May spread TB bacteria to 

others 

• Does not feel sick, but may 

become sick if the bacteria 

become active in his or her body 

• May feel sick and may have 

symptoms such as cough, 

fever, or weight loss 

• TST or IGRA results usually 

positive 

• TST or IGRA results usually 

positive 

• Chest x-ray usually normal • Chest x-ray usually abnormal 

Module 1 – Transmission and Pathogenesis of Tuberculosis 40 

LTBI vs. TB Disease (2) 

Person with LTBI Person with TB Disease 

(in the lungs) 

• Sputum smears and cultures 

negative 

• Sputum smears and cultures 

may be positive 

• Should consider treatment 

for LTBI to prevent TB 

disease 

• Needs treatment for TB 

disease 

• Does not require respiratory 

isolation 

• May require respiratory 

isolation 

• Not a case of TB • A case of TB 

Module 1 – Transmission and Pathogenesis of Tuberculosis 41 

TB Pathogenesis 

Study Question 1.7 

When a person inhales droplet nuclei containing 

M. tuberculosis, where do the droplet nuclei go? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

7
 

42 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TB Pathogenesis
 

Study Question 1.8
 

After the tubercle bacilli reach the small air 

sacs of the lung (the alveoli), what happens to 

the tubercle bacilli? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 43 

TB Pathogenesis 

Study Question 1.9 

In people with LTBI (but not TB disease), how 

does the immune system keep the tubercle 

bacilli under control? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Pathogenesis
 

Study Question 1.10
 

How is LTBI detected? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 45 

TB Pathogenesis
 

Study Question 1.11
 

What are the major similarities and differences between 

LTBI and TB disease? List characteristics of each. 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Pathogenesis 

Study Question 1.12 

What happens if the immune system cannot 

keep the tubercle bacilli under control and 

the bacilli begin to multiply rapidly? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 47 

TB Pathogenesis
 

Progression from LTBI to TB Disease
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

8
 

44 

46 

48 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Progression to TB Disease (1) 

•	 Risk of developing TB disease is highest the 

first 2 years after infection 

•	 People with LTBI can be given treatment to 

prevent them from developing TB disease 

•	 Detecting TB infection early and providing 

treatment helps prevent new cases of TB 

disease 

Module 1 – Transmission and Pathogenesis of Tuberculosis 49 

Progression to TB Disease (2) 

Some conditions increase probability of LTBI 

progressing to TB disease 

•	 Infection with HIV • Abusing drugs or alcohol or 

smoking cigarettes 

•	 History of untreated or 

inadequately treated TB disease • Silicosis 

•	 Recent TB infection (within the • Diabetes mellitus past 2 years) 

•	 Chronic renal failure •	 Immunosuppressive therapy 

such as tumor necrosis factor­ •	 Certain types of cancer (e.g., alpha (TNF) antagonists, leukemia, cancer of the head, systemic corticosteroids, or neck, or lung) immunosuppressive drug
 

therapy following organ
 

transplantation • Certain intestinal conditions
 

•	 Low body weight 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Progression to TB Disease (4)
 

TB and HIV
 

In an HIV-infected person, 

TB can develop in one of 

two ways: 

•	 Person with LTBI becomes 

infected with HIV and then 

develops TB disease as the 

immune system is weakened 

•	 Person with HIV infection 

becomes infected with M. 

tuberculosis and then 

rapidly develops TB disease 

Image credit: Mississippi State Department of Health 

Module 1 – Transmission and Pathogenesis of Tuberculosis Module 1 – Transmission and Pathogenesis of Tuberculosis 51 

Progression to TB Disease (3) 

Module 1 – Transmission and Pathogenesis of Tuberculosis 53 

Progression to TB Disease (5) 

TB and HIV 

People who are infected with both M. tuberculosis and 

HIV are much more likely to develop TB disease 

Progression to TB Disease 

Study Question 1.13 

What percentage of people who have LTBI 

(but not HIV infection) usually develop TB 

disease? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

9
 

50 

52 

54 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Progression to TB Disease 

Study Question 1.14 

What conditions appear to increase the risk that 

LTBI will progress to TB disease? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 55 

Progression to TB Disease
 

Study Question 1.15
 

How does being infected with both M. tuberculosis 

and HIV affect the risk for TB disease? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Pathogenesis
 

Sites of TB Disease 

Module 1 – Transmission and Pathogenesis of Tuberculosis 57 Module 1 – Transmission and Pathogenesis of Tuberculosis 58 

Sites of TB Disease (1) 

Bacilli may reach any part of the body, but 

common sites include: 

Sites of TB Disease (2)
 

Location Frequency 

Pulmonary TB Lungs Most TB cases are 

pulmonary 

Extrapulmonary TB Places other than 

lungs such as:

 Larynx

 Lymph nodes

 Pleura

 Brain

 Kidneys

 Bones and joints 

Found more often in: 

• HIV-infected or 

other 

immunosuppressed 

persons 

• Young children 

Disseminated TB Carried to all parts 

of body, through 

bloodstream 

Rare 

Sites for TB
 

Study Question 1.16
 

What part of the body is the most common 

site for TB disease? 

What are some other common sites? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 59 Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

10
 

56 

60 
 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

TB Pathogenesis
 

TB Classification System 

Module 1 – Transmission and Pathogenesis of Tuberculosis 61 

TB Classification System (1) 

Based on pathogenesis of TB 

Class Type Description 

0 No TB exposure 

Not infected 

No history of TB exposure 

Negative result to a TST or to an IGRA 

1 TB exposure 

No evidence of 

infection 

History of TB exposure 

Negative result to a TST or an IGRA (done 

at least 8 to 10 weeks after exposure) 

2 TB infection 

No TB disease 

Positive result to a TST or to an IGRA 

Negative smears, molecular tests, and 

cultures 

No clinical or x-ray evidence of active TB 

disease 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

TB Classification System (2) 

Based on pathogenesis of TB 

Class Type Description 

3 TB, clinically 

active 

Positive culture for M. tuberculosis OR 

Positive result to a TST or to an IGRA, and clinical, 

bacteriological, or x-ray evidence of current active 

TB disease 

4 Previous TB 

disease 

(not clinically 

active) 

Medical history of TB disease 

Abnormal but stable x-ray findings 

Positive result to a TST or to an IGRA 

Negative smears, molecular tests, and cultures (if 

done) 

No clinical or x-ray evidence of active TB disease 

5 TB 

suspected 

Signs and symptoms of TB disease, but diagnostic 

evaluation not complete 

Module 1 – Transmission and Pathogenesis of Tuberculosis 63 

TB Classification System
 

Study Question 1.17
 

What is the classification system for TB 

based on? What is it used for? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Case Studies
 

Module 1 – Transmission and Pathogenesis of Tuberculosis 65 

Module 1: Case Study 1.1 (1) 

A 30-year-old man visits the health department 

for a TST because he is required to have one 

before starting his new job as a health care 

worker. He has an 18 mm positive reaction to 

the TST. He has no symptoms of TB, and his 

chest x-ray findings are normal. 

Module 1 – Transmission and Pathogenesis of Tuberculosis 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

11
 

62 

64 

66 
 

 

 

 

 

 

Module 1: Case Study 1.1 (2) 

Should this be considered a case of TB? 

Should this man be considered infectious? 

Module 1: Case Study 1.2 (1) 

A 45-year-old woman is referred to the 

health department by her private 

physician because she was found to 

have LTBI as part of an employee testing 

program. She is overweight, with high 

blood pressure. Upon further 

questioning, she reports that she has 

injected illegal drugs in the past, but has 

never been tested for HIV infection. 

Module 1 – Transmission and Pathogenesis of Tuberculosis 67 Module 1 – Transmission and Pathogenesis of Tuberculosis 68 

Module 1: Case Study 1.2 (2) 

What conditions does this woman have that 

increase the risk that she will develop TB 

disease? 

Module 1 – Transmission and Pathogenesis of Tuberculosis 69 

Module 1 – Transmission and Pathogenesis of Tuberculosis
 

12